Ointments

Ointments belong among soft dosage forms, they are plastic gels, intended for the treatment of the skin and mucous membranes. Medicated ointments contain one or more drug substances, dispersed homogeneously in dissolved, emulsified or suspended forms.

Ointments
Plma Fehr

Other soft dosage forms:

Creams Pastes Gels or jellies Creams Certain ointments of emulsion type, which have a soft consistency and a higher water content, may be called creams.

Other soft dosage forms:

Pastes Ointments of harder consistency or those containing over 40% suspended solid are called pastes.

Gels or jellies are semisolid systems of either suspensions made up of small inorganic particles or large organic molecules interpenetrated by a liquid.

Ointments
May involve different systems ( eg. hydrocarbons, lipogels, emulsion systems, macromolecular gels) They have a well-defined colloidal structure, such as gel structure, and coherent structure. They have exactly determined characteristics such as yield value, thixotropy and plasticity which can be measured precisely.

The function of medicated ointments.

Protectives and emollients for the skin

Vehicels or bases for the topical application of medicated substances.

Medicated ointments

Grouping of ointments on the bases of effect

vehicle

Pharmacon (s)

Ointment base

auxiliary material (s)

Covering or protective ointments Ointments of wound Penetrating ointments Ointments from which the drug may be absorbed

Interaction between ointment

components and the skin:
drug

Drugs in ointments Medicated ointments may have local or general effect

Antiseptics Disinfectants Antibiotics Chemotherapeutics Antifungal drugs Antiparasitics Antiphlogistics Adsorbents Astringents Keratolytics Keratiplastics Rubefacients Antiseborrhoeics Antipsoriatics

effect

vehicle

skin

Percutaneous absorption I
Absorption through the skin is passive transport skin is impenetrable for water or drugs dissolved in water the external layers of the epidermis have a barrier function

Percutaneous absorption II this is decreased or eliminated when the external lipid layer/ film of the skin is dissolved off or the layers of stratum corneum are stripped off the absorption is essentially changed when an occlusion bandage is used

Percutaneous absorption III Drugs must display solubility in water and in lipids: drug molecules can get across the barrier when they dissolve partly in lipids and they can be absorbed after this in the deeper layers when they dissolve partly in water too.

The steps of Percutaneous absorption 1. Liberation 2. Penetration 3. Permeation

1. Liberation or drug release

2.

The second step is the penetration

This is the first step of percutaneous absorption which involves the transfer of drug from the skin surface into the stratum corneum

The molecules that have diffused to the interface get across the barrier and pass into the epidermis.

3.

The third step is the permeation

Part-processes of the drugs in the layers of skin

DRUG IN OINTMENT

LIBERATION

which is diffusion into the deeper layers

DRUG ON INTERFACE OF OINTMENT AND SKIN

PENETRATION
DRUG IN EPIDERMIS

PERMEATION
DRUG IN CORIUM AND SUBCUTIS

ABSORPTION
DRUG IN BLOOD CIRCULATION

Ointment bases In a colloidal sense, the ointments form a group of coherent systems. They may be heterogeneous and colloidal coherent systems.

Grouping of ointment bases Authors who have grouped these materials: Mnzel ( 1959) Voight (1973) Kedvessy (1981) Martin ( 1983)

Grouping of ointment bases

Bases free from water Hydrocarbons (vaselines) Lipogels Silicone gels Polyethylene glycol gels (Macrogols) Absorbent ointment bases Bases of emulsion type w/o emulsions o/w emulsions self- emulsifying waxes ambiphilic emulsion creams transparent gels of surfactants Water-soluble bases Hydrogels Synthetic materials

Bases free from water Hydrocarbons (vaselines) Lipogels Silicone gels Polyethylene glycol gels Absorbent ointment bases

Bases of emulsion type w/o emulsions o/w emulsions self- emulsifying waxes ambiphilic emulsion creams transparent gels of surfactants

Water-soluble bases Hydrogels Synthetic materials

Hydrocarbons Petrolatum (Vaselines) Natural petrolat Synthetic petrolatum

Natural petrolatum
After the distillation of crude oil, crude petrolatum remains from which petrolatum is made by cleaning with sulphuric acid. H.Ph.VII. preparations: liquid paraffin microcrystalline p. hard paraffin

Characteristics of petrolatum
It is inert chemically It does not have the capacity to emulsify water / Insoluble in water emulsifying agents Freely soluble in apolar can be used to solvents increase water absorbtion.
From a petrolatum which is liquid not suitable, separates out during storage. (number of oil or number of bleeding)

Disadvantages of petrolatum
It covers the skin hermetically, closing the pores, this can cause inflammation. It has relatively bad absorption characteristics It can be washed from the skin only with difficulty Drug liberation is very small from petrolatum.

Lipogels
fats of animal origin
(pig fat)

hydrogenated oils of vegetable origin

(hydrogenated peanut oil)

copounded lipogels oleogels

characteristics of lipogels:
coherent structure they are glycerol or fat alcohol esters of fatty acids. not body foreign chemically similar to the components of the skin the ointment film on the skin is permeable susceptible to rancidity

Lipogels I.:
pig fat ( Adeps suillus or Axungia porci )
one of the most often used lipogel bases of earlier days it is able to emulsify about 20% water it has a suitable consistency its melting point is close to the skin temperature it has a good adsorption character it becomes rancid quickly different antioxidants hinder this process (benzoic acid, propyl gallate etc.)

Lipogels II.:
hydrogenated peanut oil ( Oleum arachidis hydrogenatum) oil of vegetable origin become hard in consistency during hydrogenation made from liquid arachis oil under pressure during catalyst during storage , it hardens spontaneously

compounded lipogels liquid oils and solid prepared from lipids, 1. beeswax 2.wool fat the structure of shell 3.spermaceti is formed from the 4.oils of vegetable solid components.
origin 5.fat alcohols

Lipogels III.:

Components ofcompounded lipogels 1. waxes

solid at 20C, melt above 40C eg. Beeswax, paraffin wax

Components ofcompounded lipogels 2. wool fat ( Cera lanae)

contains cholesterol emulgent and different dissolves well in derivatives of it apolar solvents and petrolatum

Components ofcompounded lipogels 3. cetostearyl alcohol mixture of cetyl and stearyl alcohols dissolves well in oils and liquid paraffin emulgent

Components ofcompounded lipogels 4. liquid oils

form the liquid phase of lipogels sunflower oil ( Oleum helianthi) linseed oil ( Oleum lini) castor oil ( Oleum ricini) coconut oil peanut oil, olive oil, corn oil, palm oil, soya bean oil isopropyl myristate, isopropyl stearate

Lipogels IV.:
oleogels
relative new group of lipogels free from water made from colloidal silica with different oils transparent have good thermal stability and adsorption

Silicone gels
contain silicone oils used as covering and protective ointments silicone film on the skin does not hinder the respiration of the skin the skin does not lose the sensitiveness of the sense of touch coating with silicone provides resistance against water and other liquids silicones are polymers containing siloxane chains

Polyethylene glycol gels (Macrogols)

Advantages of macrogols
Water-removable bases, the can be applied to the hairy scalp too Good solvents for many pharmacons eg. benzocaine, lidocaine, resorcinol, boric acid, salicylic acid

Macrogol ointments are made via the melting of liquid and solid carbowaxes

Consistency is similar to soft paraffins Not become rancid Disperse easily on the skin Stick well to the skin Osmotic activity

Water-absorbing caracter of macrogols partly advantageous disadvantageous and partly

Example for Macrogol Unguentum Macrogoli (macrogol ointment) Ph.Hg.VII. Macrogolum 400 Macrogolum 1540

It helps the healing of wounds, but the hygroscopic character hinders the absorption of drugs

Absorbent ointment bases

the term absorbent is used here to denote the water-absorbing or emulsifying properties of these bases and not to describe their action on the skin anhydrous substances do not contain water , but if water is incorporated water- in -oil emulsion (w/o) results

Members of the group:

anhydrous lanolin and lanolin simple ointment ( Unguentum simplex) oily ointment ( Unguentum oleosum ) hydrophilic petrolatum sulphated hydrogenated castor oil

Emulsion ointment bases I w/o emulsions

absorbent ointment bases water (30-60%) Continious lipophilic phase ensures the coherent character Unguentum hydrosum

Emulsion ointment bases II

o/w emulsions Components: Emulgents of high HLB value Water (60-80%) Characteristics: Freely miscible with water Water-removable bases from the skin Must be preserved ( Sol. conservans 1-2%)

(Hydrous ointment) Ph.Hg.VII. Unguentum simplex 600,0 g Aqua destillata 400,0 g

Unguentum emolliens

(Emollient ointment) Ph.Hg.VII. Ung. Oleosum 650,0 g Aqua destillata 300,0 g Oleylum oleinicum 50,0 g

The types of o/w emulsion ointment base

Types
Creams containing stearates eg. vanishing creams, milk creams first representatives cosmetics Creams containing mixed emulgents
Components:

The components of o/w emulsion ointment base

Shell-forming materials: partial esters of glycerol or cetyl or stearyl alcohol with fatty acids Hydrophilic emulgents: sodium laurylsulphate polysorbates synthetic emulgents (Cremofor)

Lipophilic components: spermaceti waxes liquid paraffin soft paraffin

Examples for o/w emulsion ointment base

Ung. Hydrophilicum anionicum ( anionic hydrophilic ointment) Ph.Hg.VII. Ung. Emusificans anionicum Aqua destillata Ung. Hydrophilicum nonionicum ( nonionic hydrophilic ointment) Ph.Hg.VII. Ung. Emusificans nonionicum Aqua destillata

Self-emulsifying agents
Mixtures of emulgents, free from water Contains lipophilic and hydrophilic emulgent ( in ratio 9+1) From these ointment bases we can prepare the hydrophilic ointments by the addition of water

Ung. Glycerini Ung.stearini

Advantages of Self-emulsifying agents

Do not contain water, therefore they can be transported and stored in a small space Emulsifying ointments can be prepared quickly They can be made without heating Stable Ung. Emusificans anionicum Ung. Emusificans nonionicum

Water soluble bases Macromolecular hydrogels:

They contain macromolecular compounds which are of colloidal size, gel-forming materials The macromolecule take up the water by swelling

Water soluble bases Macromolecular hydrogels:

eg. Methylcellulose , hydroxyethylcellulose, carboxymethylcellulose sodium, pectin, alginates, polyacrylates and polymethacrylates inorganic colloidal materials (bentonite, colloidal silica) water (80-95%)

advantages Water soluble bases Macromolecular hydrogels:

good adhesivity excellent cooling effect in consequence of their high water content the protective film has a very good effect good drug absorption the film on the skin is transparent, it is aesthetic cheap because of the high water content

Examination of ointment bases

Physical examinations determination of solidifying point drop point tests for homogenity Tests for consistency determination of viscosity, determination of adhesion determination of the extrusion from a tube Special examination

Examination of ointment bases Physical examinations

solidifying point
with Zhukov apparatus solidifying point is the point at which the temperature decrease stops for a while or the rate of decrease is less than 0,1C per minute

drop point
with Ubbelohde thermometer the drop point is the temperature at which a solid becomes droppable under given conditions

Examination of ointment bases

Tests for homogenity ointments must be homogeneous, no coherent particles, droplets or lumps must be observed on inspection at a fourfold magnification of the ointment spread in a thin layer over a microslide. Ointment must not be rancid.

Examination of ointment bases

Tests for consistency rotational viscosimetry eg. Rotovisco determination of flow curves of ointments, the structural viscosity and the thixotropy consistometry consistometers are the testing apparatus in which a solid test body penetrates into the ointment and the rate of the penetration can be determined numerically

Examination of ointment bases penetrometers instruments for the the penetration measurement of the occurring in a fixed consistency or time is determined, hardness of relatively the distance rigid semisolids travelled is usually reported in the double cone form is decimillimeters the most commonly (10-4 meters) used in pharmacy

Examination of ointment bases determination of viscosity, structural viscosity plastic viscosity thixotrophy rheopexy dilatant behaviour etc.

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Examination of ointment bases

extensometers

Examination of ointment bases

are used to determine the spreading properties of medicated ointments extenso-balances available have become

determination of adhesion the ointment film is between two slides, on one of which a force is acting.

determination of the extrusion from a tube also gives useful results.

Special examination method

water absorbing capacity and water retaining capacity of ointments containing water

Stability of ointment bases and ointments

Physical and consistency changes Chemical changes Microbiological changes

water number:
100 mw ----------mo mw = mass of water absorbed in ointment (g) mo = mass of ointment (g)

w=

Physical and consistency changes Syneresis

Occurs when the The quantitive ointment base parameter of this contracts and liquid process is the oil separates from it number: quantity (bleeding of vaseline) of liquid freed during heating or The reason for this lies mechanical loading in the unstable nature of the structure.

Chemical change Rancidization

It can be detected with the organs of sense (colour, smell, taste) Many products come into being Fatty acids decompose Antioxidants

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Micobiological preservatives
Ointments containing much water (hydrogels, o/w type emulsion ointments) must be microbiologically preserved. Nipagins, chlorobutanol, sorbic acid

Choice of ointment bases I.

We must take into consideration the properties of the pharmacon (s) and the diagnosis. It is practical to choose hydrocarbon bases when we want to attain a surface effect or the medicament has a skin-stimulative effect Lipogels are advised when the drug dissolves in fatty materials and it is desirable to achieve an extensive effect

Choice of ointment bases II.

Macrogols are used when the effective material dissolves in them and the patient is sensitive to lipids It is reasonable to use a w/o emulsion ointment base when the pharmacon dissolves in water or in lipids and it is wished to achieve a slow but prolonged release

Choice of ointment bases III. When the drug dissolves in water o/w emulsion ointment bases are used And finally, hydrogel bases are used when the pharmacon dissolves very well in water or the patient is sensitive to lipids

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